Sun-Mi Park, Hyunwoo Cho, Angela M Thornton, Trevor S Barlowe, Timothy Chou, Sagar Chhangawala, Lauren Fairchild, James Taggart, Arthur Chow, Alexandria Schurer, Antoine Gruet, Matthew D Witkin, Jun Hyun Kim, Ethan M Shevach, Andrei Krivtsov, Scott A Armstrong, Christina Leslie, Michael G Kharas
Leukemias exhibit a dysregulated developmental program mediated through both genetic and epigenetic mechanisms. Although IKZF2 is expressed in hematopoietic stem cells (HSCs), we found that it is dispensable for mouse and human HSC function. In contrast to its role as a tumor suppressor in hypodiploid B-acute lymphoblastic leukemia, we found that IKZF2 is required for myeloid leukemia. IKZF2 is highly expressed in leukemic stem cells (LSCs), and its deficiency results in defective LSC function. IKZF2 depletion in acute myeloid leukemia (AML) cells reduced colony formation, increased differentiation and apoptosis, and delayed leukemogenesis...
January 3, 2019: Cell Stem Cell